Chan I T, Limmer A, Louie M C, Bullock E D, Fung-Leung W P, Mak T W, Loh D Y
Howard Hughes Medical Institute, Department of Medicine, Genetics, and Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110.
Science. 1993 Sep 17;261(5128):1581-4. doi: 10.1126/science.8372352.
The CD8 alpha cytoplasmic domain associates with p56lck, a nonreceptor protein-tyrosine kinase. The biological relevance of CD8 alpha-Lck association in T cell development was tested with transgenic mice generated to express a CD8 alpha molecule with two amino acid substitutions in its cytoplasmic domain, which abolishes the association of CD8 alpha with Lck. The CD8 alpha mutant was analyzed in a CD8-/- background and in the context of the transgenic 2C T cell receptor. The development and function of CD8+ T cells in these mice were apparently normal. Thus, CD8 alpha-Lck association is not necessary for positive selection, negative selection, or CD8-dependent cytotoxic function.
CD8α胞质结构域与p56lck(一种非受体蛋白酪氨酸激酶)相关联。通过生成转基因小鼠来测试CD8α-Lck关联在T细胞发育中的生物学相关性,这些转基因小鼠表达的CD8α分子在其胞质结构域中有两个氨基酸替换,这消除了CD8α与Lck的关联。在CD8 - / - 背景下并结合转基因2C T细胞受体对CD8α突变体进行了分析。这些小鼠中CD8 + T细胞的发育和功能显然正常。因此,CD8α-Lck关联对于阳性选择、阴性选择或CD8依赖性细胞毒性功能并非必需。